Rabies virus antigenicity: an overview.

Rabies virus contains a negative stranded RNA genome and belongs to the family Rhabdoviridae. The genome codes for five structural proteins, of which one, the glycoprotein, is the only external protein of the virion. It is a protein of 505 amino acids with a signal peptide cleared in the endoplasmic reticulum, an ectodomain of 439 amino acids, a transmembra~e region of 22 amino acids and a cytoplasmic port1on of 44 amino acids. The glycoprotein of the CVS strain, the laboratory strain used in all our experiments, has two sites of glycosylation at positions 204 and 319. Because of its position in the virion, the glycoprotein plays an important role during the cycle of infection. The first is the recognition of target cells which determines the tropism of the virus. While many cell lines are permissive for rabies virus, in anim~ls the virus infects neurones almost exclusively. Th1s means that it recognizes a specific receptor(s) at the surface of these cells and that this recognition is mediated by the glycoprotein. Another important role of the glycoprotein is the stimulation of the immune system. In addition to its role in cell-mediated immunity, the glycoprotein stimulates the synthesis of circulating antibodies and most of these antibodies neutralize the infectivity of the virus. The development of hybridoma technology made possible the use of the neutralizing power of anti-glycoprotein monoclonal antibodies (Mab) to isolate antigenic mutants which resist neutralization. The study of these mutants, associated with an analysis of their reactivity patterns with Mabs, provides an indication as to the location of antigenic sites at the surface of the glycoprotein. Furthermore, this methodology has been widely used for the study of the antigenicity of viral proteins.